‘Psoriasis 1’ reduces psoriasis‑like skin inflammation by inhibiting the VDR‑mediated nuclear NF‑κB and STAT signaling pathways

Sun,Wen; Gao,Yang; Yu,Xianhua; Yuan,Yuan; Yi,Jun; Zhang,Zhen; Cheng,Yuxing; Li,Yong; Peng,Xing; Cha,Xushan

doi:10.3892/mmr.2018.9262

‘Psoriasis 1’ reduces psoriasis‑like skin inflammation by inhibiting the VDR‑mediated nuclear NF‑κB and STAT signaling pathways

Authors:
- Wen Sun
- Yang Gao
- Xianhua Yu
- Yuan Yuan
- Jun Yi
- Zhen Zhang
- Yuxing Cheng
- Yong Li
- Xing Peng
- Xushan Cha
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Affiliations: Department of Dermatology, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Department of Anesthesiology, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China, Department of Vascular Surgery, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China, Department of Spine Surgery, Shenzhen Baoan Shajing People's Hospital, Shenzhen, Guangdong 518104, P.R. China, Department of Surgery, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Department of Dermatology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
Published online on: July 9, 2018 https://doi.org/10.3892/mmr.2018.9262
Pages: 2733-2743
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

‘Psoriasis 1’, a Chinese herbal medicine (CHM) formulation, is extensively used to treat psoriasis in China. Although this CHM formulation yields good therapeutic effect, the underlying mechanism of how this works remains unknown. The present study aimed to test the hypothesis that the CHM formulation ‘psoriasis 1’ inhibits vitamin D receptor (VDR)‑mediated inflammation in psoriasis. To test this, a model of psoriasis was established by stimulating keratinocytes (HaCaT cells) with tumor necrosis factor (TNF)‑α; these cells were subsequently transfected with a lentiviral VDR RNA interference expression vector. The expression levels of 25‑hydroxyvitamin D3 (25HVD3), TNF‑α, interleukin (IL)‑4, IL‑1, IL‑17C, IL‑23 and IL‑6 were measured using ELISA, and the expression levels of VDR, inhibitor of nuclear factor (NF)‑κB (IKK), NF‑κB, signal transducer and activator of transcription (STAT) 3 and STAT4 were measured using reverse transcription‑quantitative polymerase chain reaction analysis and western blotting. It was observed that ‘psoriasis 1’ downregulated the concentrations of TNF‑α, IFN‑γ, IL‑22, IL‑17C, IL‑1β and IL‑4, and upregulated the concentration of 25HVD3; furthermore, ‘psoriasis 1’ downregulated the expression levels of NF‑κB, phosphorylated (p)‑NF‑κB, IKK, p‑IKK, STAT3, p‑STAT3, STAT4 and p‑STAT4, and upregulated the expression level of VDR in TNF‑α‑induced HaCaT cells. These results suggested that ‘psoriasis 1’ suppressed the inflammatory response and the activation of the NF‑κB and STAT signaling pathways. In addition, it was identified that silencing VDR expression decreased the levels of TNF‑α, IFN‑γ, IL‑22, IL‑17C, IL‑1β and IL‑4, and increased the level of 25HVD3; silencing VDR expression additionally downregulated the expression levels of NF‑кB, p‑NF‑кB, IKK, p‑IKK, STAT3, p‑STAT3, STAT4 and p‑STAT4, and upregulated the level of VDR in TNF‑α‑induced HaCaT cells. It was concluded that ‘psoriasis 1’ exerts inflammation‑suppressive effects in psoriasis by suppressing the NF‑кB and STAT signaling pathways.

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